scholarly journals Presynaptic NMDA receptor-mediated modulation of excitatory neurotransmission in the mouse dorsal motor nucleus of the vagus

2012 ◽  
Vol 108 (5) ◽  
pp. 1484-1491 ◽  
Author(s):  
Eva C. Bach ◽  
Bret N. Smith
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Synaptic Input ◽  
Gaba Release ◽  
Brain Regions ◽  
Motor Nucleus ◽  
Current Frequency ◽  
Receptor Modulation ◽  
Dorsal Motor Nucleus ◽  
Presynaptic Nmda Receptors

Activity of neurons in the dorsal motor nucleus of the vagus nerve (DMV) is closely regulated by synaptic input, and regulation of that input by glutamate receptors on presynaptic terminals has been proposed. Presynaptic N-methyl-d-aspartic acid (NMDA) receptors have been identified in a number of brain regions and act to modulate neurotransmitter release, but functional presynaptic NMDA receptors have not been adequately studied in the DMV. This study identified the presence and physiological function of presynaptic NMDA receptors on synaptic input to DMV neurons. Whole-cell patch-clamp recordings from DMV neurons in acute slices from mice revealed prevalent miniature excitatory postsynaptic currents, which were significantly increased in frequency, but not amplitude, by application of NMDA. Antagonism of NMDA receptors with dl-2-amino-5-phosphonopentanoic acid (100 μM) resulted in a decrease in miniature excitatory postsynaptic current frequency and an increase in the paired pulse ratio of responses following afferent stimulation. No consistent effects of presynaptic NMDA receptor modulation were observed on GABAergic inputs. These results suggest that presynaptic NMDA receptors are present in the dorsal vagal complex and function to facilitate the release of glutamate, preferentially onto DMV neurons tonically, with little effect on GABA release. This type of presynaptic modulation represents a potentially novel form of glutamate regulation in the DMV, which may function to regulate glutamate-induced activity of central parasympathetic circuits.

Role of adenosine in NMDA receptor modulation in the cerebral cortex of an anoxia-tolerant turtle (Chrysemys picta belli).

1995 ◽  
Vol 198 (7) ◽  
pp. 1621-1628 ◽  
Author(s):  
L T Buck ◽  
P E Bickler
Keyword(s):  
Cerebral Cortex ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Control Level ◽  
Chrysemys Picta ◽  
Receptor Modulation ◽  
A1 Receptor ◽  
Excitatory Neurotransmission ◽  
Similar Decrease

Accumulation of the neuromodulator adenosine in the anoxia-tolerant turtle brain may play a key role in a protective decrease in excitatory neurotransmission during anoxia. Since excitatory neurotransmission is mediated largely by Ca2+ entry through N-methyl-D-aspartate (NMDA) receptors, we measured the effect of adenosine on NMDA-mediated Ca2+ transients in normoxic and anoxic turtle cerebrocortical sheets. Intracellular [Ca2+] was measured fluorometrically with the Ca2+-sensitive dye Fura-2. Baseline intracellular [Ca2+] and [ATP] were also measured to assess cortical sheet viability and potential toxic effects of NMDA. Baseline [Ca2+] did not change significantly under any condition, ranging from 109 +/- 22 to 187 +/- 26 nmoll-1. Throughout normoxic and 2h anoxic protocols, and after single and multiple NMDA exposures, [ATP] did not change significantly, ranging from 16.0 +/- 1.9 to 25.3 +/- 4.9 nmol ATP mg-1 protein. Adenosine caused a reduction in the normoxic NMDA-mediated increase in [Ca2+] from a control level of 287 +/- 35 to 103 +/- 22 nmoll-1 (64%). This effect is mediated by the A1 receptor since 8-phenyltheophylline (a specific A1 antagonist) effectively blocked the adenosine effect and N6-cyclopentyladenosine (a specific A1 agonist) elicited a similar decrease in the NMDA-mediated response. Cortical sheets exposed to anoxia alone exhibited a 52% decrease in the NMDA-mediated [Ca2+] rise, from 232 +/- 30 to 111 +/- 9 nmoll-1. The addition of adenosine had no further effect and 8-phenyltheophylline did not antagonize the observed decrease. Therefore, the observed down-regulation of NMDA receptor activity during anoxia must involve additional, as yet unknown, mechanisms.

scholarly journals NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21)

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Xin Zhang ◽  
Bin Cheng ◽  
Xianghong Jing ◽  
Yongfa Qiao ◽  
Xinyan Gao ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Nmda Receptor ◽  
Ampa Receptor ◽  
Gastrointestinal Motility ◽  
Kynurenic Acid ◽  
Basic Mechanism ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Lines Of Evidence

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

Glutamate Mediates an Excitatory Influence of the Paraventricular Hypothalamic Nucleus on the Dorsal Motor Nucleus of the Vagus

2002 ◽  
Vol 88 (1) ◽  
pp. 49-63 ◽  
Author(s):  
Xueguo Zhang ◽  
Ronald Fogel
Keyword(s):  
Nmda Receptor ◽  
Firing Rate ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Kynurenic Acid ◽  
Electrical Current ◽  
The Other ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Stimulation Of

Data have shown that the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) play important roles in the regulation of gastrointestinal function and eating behavior. Anatomical studies have demonstrated direct projections from the PVN to the DMNV and physiological studies showed that the DMNV mediates many of the effects of PVN stimulation and electrical current stimulation of the PVN excites a subset of DMNV neurons. The aim of this study was to characterize the role of glutamate receptors in the excitatory influence of the PVN on gut-related DMNV neurons. Using single-cell recording techniques, we determined the effects of kynurenic acid, 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), anddl-2-amino-5-phosphonopentanoic acid (dl-AP5) on the increase in firing rate due to electrical current stimulation of the PVN. In initial experiments, we studied 24 DMNV neurons excited by electrical current stimulation of the PVN. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, prevented the PVN effect in 22 neurons and significantly attenuated the effect in the other cells. Nine of these neurons demonstrated an inhibition in firing rate with PVN stimulation after pretreatment with kynurenic acid. In a separate group of 12 neurons, we determined the effects of CNQX (1.2 nmol) injected into the DMNV. This AMPA receptor antagonist completely blocked the excitatory response to PVN stimulation of six DMNV neurons and significantly attenuated the response of the other six DMNV neurons. The addition of 1.2 nmol dl-AP5, a N-methyl-d-aspartate (NMDA) receptor antagonist, further attenuated the response to PVN stimulation in four of the five DMNV neurons that were still excited after CNQX treatment. The fifth neuron demonstrated PVN- induced inhibition of firing rate after treatment with CNQX and dl-AP5. In a separate group of 11 DMNV neurons excited by electrical stimulation of the PVN,dl-AP5 partially attenuated the excitatory responses of only four DMNV neurons and did not block the excitation of any cells. The mean latency (14 neurons tested) from the PVN to the DMNV was 37.71 ± 2.40 (SE) ms. Monosynaptic action potentials and excitatory postsynaptic potentials were demonstrated in three DMNV neurons by intracellular recording. Our results indicate that glutamate released from PVN neurons projecting to the DMNV excite the gut-related vagal motor neurons by acting predominantly on the AMPA receptor. The NMDA receptor plays only a minor role in the excitatory effect.

scholarly journals Input-output signal processing plasticity of vagal motorneurons in response to cardiac ischemic injury

2020 ◽  
Author(s):  
Jonathan Gorky ◽  
Alison Moss ◽  
Marina Balycheva ◽  
Rajanikanth Vadigepalli ◽  
James S. Schwaber
Keyword(s):  
Signal Processing ◽  
Output Signal ◽  
Ischemic Injury ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Motor Nucleus ◽  
Input Output ◽  
Dorsal Motor Nucleus ◽  
Transcriptomics Data ◽  
Dramatic Shift

AbstractVagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease. The neuronal molecular phenotypes in the dorsal motor nucleus of the vagus (DMV) remain largely unexplored, limiting the potential for harnessing the DMV plasticity for therapeutic interventions. We developed a mesoscale single cell transcriptomics data from hundreds of DMV neurons under homeostasis and following physiological perturbations. Our results revealed that homeostatic DMV neuronal states can be organized into distinguishable input-output signal processing units. Remote ischemic preconditioning induced a distinctive shift in the neuronal states towards diminishing the role of inhibitory inputs, with concomitant changes in regulatory microRNAs miR-218a and miR-495. Chronic cardiac ischemic injury resulted in a dramatic shift in DMV neuronal states suggestive of enhanced neurosecretory function. We propose a DMV molecular network mechanism that integrates combinatorial neurotransmitter inputs from multiple brain regions and humoral signals to modulate cardiac health.

Oxytocin microinjected into dorsal motor nucleus of the vagus excites gallbladder motility via NMDA receptor–NO-cGMP pathway

2005 ◽  
Vol 1032 (1-2) ◽  
pp. 116-122 ◽  
Author(s):  
Chuan Yong Liu ◽  
Dong Ping Xie ◽  
Ke Jing Liu ◽  
Yu Qin Zhou ◽  
Jing Zhang Liu
Keyword(s):  
Nmda Receptor ◽  
Gallbladder Motility ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Cgmp Pathway

scholarly journals Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals

1999 ◽  
Vol 277 (4) ◽  
pp. R1104-R1111 ◽  
Author(s):  
Huiyuan Zheng ◽  
Lisa Kelly ◽  
Laurel M. Patterson ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Nmda Receptor ◽  
Area Postrema ◽  
Additive Model ◽  
Nmda Receptor Antagonist ◽  
Gastric Distension ◽  
Motor Nucleus ◽  
Sucrose Intake ◽  
Mk 801 ◽  
Dorsal Motor Nucleus ◽  
Fos Expression

To test the possible role of N-methyl-d-aspartate (NMDA) glutamate receptors in the transmission of gastrointestinal satiety signals at the level of the nucleus of the solitary tract (NTS), we assessed the effect of fourth ventricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on short-term sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not affecting initial rate of intake, significantly increased sucrose intake during the later phase of the meal (10–30 min, 8.9 ± 1.0 vs. 2.9 ± 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the dorsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produced significant Fos expression and significantly reduced (−75%, P < 0.05) the ability of gastric distension to induce Fos expression, assuming an additive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-mediated glutamatergic transmission of vagal satiety signals in general, they lend limited support for such a role in the transmission of specific gastric distension signals.

scholarly journals Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

2019 ◽  
Author(s):  
Alastair J. MacDonald ◽  
Fiona E. Holmes ◽  
Craig Beall ◽  
Anthony E. Pickering ◽  
Kate L.J. Ellacott
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Active Role ◽  
Brain Regions ◽  
Negative Energy ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Structural Support ◽  
Dorsal Motor Nucleus ◽  
Hypothalamic Arcuate Nucleus

Food intake is controlled by the coordinated action of numerous brain regions but a complete understanding remains elusive. Of these brain regions the brainstem dorsal vagal complex (DVC) is the first site for integration of visceral synaptic and hormonal cues that act to inhibit food intake. The DVC consists of three nuclei: the nucleus of the solitary tract (NTS), area postrema (AP) and dorsal motor nucleus of the vagus (DMX). Targeted chemogenetic activation of appetite-responsive NTS neuronal populations causes short term decreases in food intake. Astrocytes are a class of glial cell which provide metabolic and structural support to neurons and play an active role in modulating neurotransmission. Within the hypothalamic arcuate nucleus (ARC) astrocytes are regulated by both positive and negative energy balance and express receptors for hormones that influence satiety and hunger. Chemogenetic activation of these ARC astrocytes alters food intake. Since NTS astrocytes respond to vagal stimulation, we hypothesised that they may be involved in mediating satiety. Here we show that NTS astrocytes show plastic alterations in morphology following excess food consumption and that chemogenetic activation of DVC astrocytes causes a decrease in food intake, by recruiting an appetite-inhibiting circuit, without producing aversion. These findings are the first using genetically-targeted manipulation of DVC astrocytes to demonstrate their role in the brain’s regulation of food intake.

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